1. Field of Invention
The invention relates to treatment of psychiatric or neurological symptoms that may or may not relate to an underlying psychiatric disorder recognized in the DSM 5.0, e.g., Autistic Spectrum Disorder, Anxiety, Obsessive-Compulsive Disorder. More particularly, the invention relates to administering to a person having one or more symptoms whether or not related to an underlying psychiatric and/or neurological condition) that respond to therapeutic doses of inositol provided in a plurality of comestible units, e.g., cookies. Such symptoms may include, among others, anxiety, hypersensitivity, restricted areas of interest, repetitive behaviors, irritability and emotional lability.
2. Description of Related Art
When a psychiatrist is presented with a patient exhibiting one or more behaviors such as poor social skills, defiance, lack of patience, difficulty paying attention, ritualistic behavior and/or mood swings, where such behavior(s) interferes with normal functioning, the psychiatrist must first make a diagnosis before formulating a treatment plan.
Today, the psychiatrist's nomenclature, i.e., the criteria for psychiatric evaluation and classification is provided in the Diagnostic and Statistical Manual of Mental Disorders (“DSM”), a periodically revised psychiatric “Bible” published by the American Psychiatric Association. The current version of the DSM is DSM 5.0, which was published on May 18, 2013.
The psychiatrist's professional judgment in rendering a diagnosis is largely informed by the criteria for various disorders set forth in the DSM. Thus, a psychiatrist presented with a patient exhibiting any such symptoms as those described above would consult the DSM in rendering a diagnosis. The diagnosis would, in turn, inform a treatment program. Whether a given patient is determined, for example, to have AMID as opposed to Hypomania in Bipolar Disorder, depends on whether the patient's symptoms comport with criteria set forth for these conditions in the DSM. Proper diagnosis is critical since a wrong diagnosis will likely lead to an ineffective or even potentially harmful treatment program.
The DSM 5.0 definition of Autism Spectrum Disorder (“ASD”) is as follows:                A. Persistent deficits in social communication and social interaction across contexts, not accounted for by general developmental delays, and manifest by all 3 of the following:                    1. Deficits in social-emotional reciprocity: ranging from abnormal social approach and failure of normal back and forth conversation through reduced sharing of interests, emotions, and affects and response to total lack of initiation of social interaction.            2. Deficits in nonverbal communicative behaviors used for social interaction: ranging from poorly integrated verbal and nonverbal communication, through abnormalities in eye contact and body language, or deficits in understanding and use of nonverbal communication, to total lack of facial expression or gestures.            3. Deficits in developing and maintaining relationships appropriate to developmental level (beyond those of caregivers); ranging from difficulties to adjusting behavior to suit different social contexts through difficulties in sharing imaginative play and in making friends to an apparent absence of interest in people.                        B. Restricted, repetitive patterns of behavior, interests, or activities as manifested by at least two of the following:                    1. Stereotyped or repetitive speech, motor movements, or use of objects such as simple motor stereotypes, echolalia, repetitive use of objects, or idiosyncratic phrases).            2. Excessive adherence to routines, ritualized patterns of verbal or nonverbal behavior, or excessive resistance to change such as motoric rituals, insistence on same route or food, repetitive questioning or extreme distress at small changes).            3. Highly restricted, fixated interests that are abnormal in intensity or focus (such as strong attachment to or preoccupation with unusual objects, excessively circumscribed or perseverative interests).            4. Hyper- or hypo-reactivity to sensory input or unusual interest in sensory aspects of environment (such as apparent indifference to pain/heat/cold, adverse response to specific sounds or textures, excessive smelling or touching of objects, fascination with lights or spinning objects).                        C. Symptoms must be present in early childhood (but may not become fully manifest until social demands exceed limited capacities).        D. Symptoms together limit and impair everyday functioning.        
Part A of the DSM 5.0 definition of ASD and Part B of the DSM 5.0 definition of ASD are hereinafter collectively referred to as “core symptoms” of ASD or “core ASD symptoms,” since they are, by definition, present in all ASD patients. Throughout this specification, the constituent symptoms of the core symptoms of ASD may be individually referred to respectively as “part A of the DSM 5.0 definition of ASD” and “part B of the DSM 5.0 definition of ASD.”
Other symptoms that may be manifest in ASD patients and which are associated with their ASD are referred to herein as “associated symptoms” of ASD or “associated ASD symptoms”. Such associated symptoms of ASD may include at least one of the following: impulsivity, concentration deficit or attention deficit and emotional lability/irritability. As discussed below, as relates to an optional aspect of the invention, emotional lability/irritability may also manifest itself in patients with a different underlying condition or with no particular diagnosed underlying condition.
The term “impulsivity,” as used herein, is characterized by the following: often blurts out answers before questions have been completed and/or often has difficulty waiting for his/her turn and/or often interrupts or intrudes on others (e.g., butts into conversations or games).
The terms “concentration deficit” and “attention deficit” are synonymous with each other and are therefore interchangeable. As used herein, the terms “concentration deficit” and “attention deficit” are characterized by the following: deficits in concentration as evidenced by often having difficulty sustaining attention in tasks or play activities, often does not seem to listen when spoken to directly, is often easily distracted by extraneous stimuli.
The terms “emotional lability” and “irritability,” are synonymous with each other and are therefore interchangeable. As used herein, “emotional lability” and “irritability” are compounded into the single term (which is synonymous with each individual term): “emotional lability/irritability.” Emotional lability/irritability is characterized by the following: severe, reactive mood swings in response to real or perceived situations where demanded needs are not being met in the environment. Emotional lability/irritability may optionally be measured using the Aberrant Behavior Checklist irritability subscale.
The Applicant has discovered a pervasive subpopulation within ASD that responds particularly well to a combination therapy that the Applicant has invented. In addition to the core symptoms of DSM 5.0 ASD, defined above, the Applicant has found patients in this subpopulation have one or more (usually all) associated symptoms of ASD, as defined above (i.e., impulsivity, concentration deficit or attention deficit and/or emotional lability/irritability). The combination therapy to treat ASD that Applicant invented, namely administering a therapeutically effective amount of an alpha-2 adrenergic agonist in an extended release dosage form in combination with a therapeutically effective amount of inositol, is described in detail in the following of Applicant's patent applications, all of which are incorporated by reference herein in their entireties: WO 2014/168820 and U.S. Pat. Pub. Nos. 2014/0309271, 2014/0309270 and 2014/0309269.
Based on Applicant's experience and insights, the aforementioned combination therapy is a superior treatment for ASD compared to use of either agent alone. For example, neither agent alone is effective in treating all core symptoms of ASD and associated symptoms of ASD, whereas the combination is effective in treating all such symptoms. Moreover, Applicant has found that the combination exhibits a synergistic effect in treating Part A of the DSM 5.0 definition of ASD and emotional lability/irritability.
Notwithstanding the superior efficacy of the combination over administration of either agent alone in ASD, monotherapy with only one of these agents is still far more effective than either doing nothing or administering other known drugs. Applicant has seen cases in which ASD patients were misdiagnosed based on patients' presenting associated symptoms of ASD, which treating physicians misinterpreted as being indicative of underlying conditions unrelated to ASD. Such misdiagnoses led to prescribing drugs that either did not help, or exacerbated these patients' symptoms, and/or caused serious side effects. Such drugs included psychostimulants, Strattera, Wellbutrin, Provigil, Nuvigil, Tenex, propranonol, selective serotonin re-uptake inhibitors, serotonin and norepinephrine reuptake inhibitors, mood stabilizers and atypical antipsychotics. See, e.g., Examples 1 and 2 of Applicant's U.S. Pat. Pub. 2014/0309270.
Whereas the aforementioned drugs were found to be ineffective or harmful to ASD patients, Applicant has found that an extended release alpha-2 adrenergic agonist, such as extended release clonidine (e.g., marketed as KAPVAY®) or extended release guanfacine (e.g., marketed as INTUNIV®) as monotherapy for ASD is effective in treating some ASD symptoms. Likewise, Applicant has found that high doses of inositol are effective as a monotherapy in treating some ASD symptoms. While Applicant's combination therapy is superior and preferred for treating ASD over monotherapy using either agent alone, such monotherapy is still an improvement over anything else known to Applicant (aside of course from Applicant's combination therapy). Given the urgency of the health need for effective ASD treatment, and the fact that regulatory approval of any new drug (in this case, the combination therapy) generally takes years, there is a need for a readily available treatment for ASD patients.
Inositol is a natural supplement that is already widely available, e.g., in vitamin stores, without a prescription. Applicant has discovered that high doses of inositol are safe and effective in treating Part B of the DSM 5.0 definition of ASD and the associated symptom of ASD of emotional lability/irritability. Alleviation of these symptoms alone would provide some relief to ASD patients and their caretakers. While there are exceptions, Applicant has found that therapeutic doses of inositol for ASD patients tend to be about 9,000 mg to about 32,400 mg per day, more typically about 18,000 mg to about 32,400 mg per day. Inositol is typically available as a supplement, e.g., in powder form. Given the large amounts of inositol generally necessary to provide therapeutic doses to ASD patients, such commercially available inositol is not typically administered orally without being mixed with some other substance. For example, inositol is typically mixed into a drink or semi solid food, e.g., applesauce.
However, Applicant has found that children sometimes do not respond well to taking large doses of inositol mixed in a drink. Large amounts of inositol, e.g., 9,000 mg to 32,400 mg per day, may be difficult for parents to premeasure with precision and to carry in the standard large bottles that contain the inositol powder when the child is not home. Some may opt to carry premeasured doses of inositol in, e.g., sandwich bags or the like, when on the go. However, this may appear suspicious, since the powder has the visual appearance of cocaine. Moreover, children also may refuse to finish the drink or food into which the inositol is mixed or refuse to eat/drink the mixture altogether when the child realizes that he/she is consuming medication. The bottom line is that pharmacotherapy is not effective if it cannot be administered and inositol in its typical commercial form can be problematic in this regard.
There is thus a need for an improved method for delivering high doses of inositol to a patient in need thereof. This need extends to any such patients, whether suffering from a DSM 5.0 recognized psychiatric condition (e.g., ASD) or not. For example, whether or not symptomology is rooted in ASD, a different condition, or no recognized or diagnosed underlying condition, there is a need for an improved method for delivering high doses of inositol in patients exhibiting one or more of the following symptoms: anxiety, hypersensitivity, restricted areas of interest, repetitive behaviors, irritability and emotional lability.